New research published in Ophthalmology Science evaluated the use of electroretinography (ERG) / pupillometry compared to three forms of functional testing in identifying diabetic retinopathy (DR) patients at the highest risk for developing vision-threatening complications (VTC).
The results revealed strong findings favoring the only FDA-cleared medical device for ERG testing.
Let’s start with the basics: ERG.
ERG is a noninvasive and objective test that measures the retina’s electrical activity in response to a light stimulus to determine the function of:
- Photoreceptor cells
- Inner retina cells
- Ganglion cells
And, far more critically: This test is also instrumental in providing early detection of retinal dysfunction.
Wasn’t there a recent announcement about ERG by the AAO?
Indeed there was. Earlier this year, the American Academy of Ophthalmology (AAO) added ERG to its 2024 update of Preferred Practice Pattern Guidelines (PPP)—considered the gold standard for clinical decision-making—for DR.
- See here for details on that
And what led to this addition?
The 2015 FDA 510(k) clearance of the first-ever handheld ERG/visual evoked potentials (VEP) device: the RETeval (by LKC Technologies).
What it does: Allows clinicians to detect functional stress within the retina and optic nerve pathways to provide objective information—enabling earlier detection, prediction, follow-up, and monitoring of retina and optic nerve diseases.
Among its disease targets:
- DR (and other ischemic conditions)
- Glaucoma
- Optic nerve neuropathies
- Pediatric diseases
- Suspected inherited retinal diseases (IRDs)
How does the device work?
Check out a visual of the process, which combines ERG and pupil response for DR scoring and uses noninvasive sensor strip skin electrodes to prevent corneal contact.
As for the test it performs (aside from DR assessments), see here.
- Notably: Test times range anywhere from 20 seconds to 1 minute and 15 seconds.
Alrighty, now to this new research.
Conducted as a longitudinal prospective study at 44 clinical locations across the United States, investigators evaluated the performance of 56 parameters from four testing modalities in predicting the risk for VTCs among a subset of DR patients.
- The participants: 162 patients (aged 18 to 80; mean age: 57; 58% male) diagnosed with moderate-to-severe nonproliferative diabetic retinopathy (NPDR) and no center-involved diabetic macular edema (DME)
- Those testing modalities (obtained from a prior study):
- ERG/pupillometry (n = 74; 307 eyes)
- Color fundus photography (FP) (n = 162; 140 eyes)
- Optical coherence tomography angiography (OCTA) (n = 73; 131 eyes)
- Ultra-widefield fluorescein angiography (UWF-FA) (n = 101; 101 eyes)
- The setup: Patients underwent a comprehensive ocular assessment every 12 weeks that included: dilated slit lamp biomicroscopy; intraocular pressure (IOP); dilated indirect ophthalmoscopy; spectral-domain OCT; 7-field FP; and FA (only at weeks 0, 24, and 48)
- The duration: 48 weeks in total
And how was disease progression determined?
Progression to proliferative DR (PDR) or DME (through VTCs) was identified by meeting any of the following:
- DR severity scale of 61+ (PDR)
- Investigator report of a PDR adverse event (AE)
- Eye treated by laser or anti-vascular endothelial growth factor (VEGF) intravitreal (IVT) injection
- ≥20% increase in central subfield thickness (CST)
- Investigator report of a DME AE (confirmed by a reading center)
Anything to keep in mind regarding this setup?
A few items.
- Those endpoints (in the previous section) were grouped together because they “either indicate(d) the need for treatment or that treatment was performed”
- Each of the 56 parameters included a “high” or “low” relative risk (RR) for progression
- Kaplan-Meier analysis and a Cox proportional hazards model were applied to each of the 56 parameters to identify significant predictors of VTC progression
So what was found?
See below for a look at the number of participants and their respective eyes (including total percentages) who progressed to DR or DME for each assigned modality.
- FP: 56 patients, 71 eyes (23.1%)
- ERG/pupillometry: 27 patients, 35 eyes (25.0%)
- OCTA: 23 patients, 29 eyes (22.1%)
- UWFA-FA: 19 patients, 19 eyes (18.8%)
… meaning?
Of the 56 parameters, ERG/pupillometry (the RETeval DR score) was found to be the strongest predictor of disease progression after 48 weeks.
- The DR score: ≥26.9 with a RR of 5.6 (p < 0.0001)
How did this compare to the other testing modalities?
For those, the most predictive parameters were:
- UWF-FA: total ischemia index of ≥0.125 with an RR of 5.3 (p < 0.0001)
- OCTA: foveal avascular zone area of ≥0.295 mm2 with an RR of 3.6 (p < 0.05)
- FP: DR severity scale ≥47 (moderate NPDR) with an RR of 2.1 (p < 0.05)
What did investigators conclude?
The generalized finding: Both forms of testing (functional using ERG and pupil response as well as structural using those three other modalities) are capable of predicting progression to VTC from DR.
However: The DR score (obtained via the RETeval device) had the best predictive capability.
“These results suggest it is possible to improve the DR staging system, which in turn may enable better allocation of health care resources," the study authors wrote.